Hodgkin's disease (HD) is a common lymphoid neoplasm, chiefly of adolescents and young adults, but also seen in later life. Although great therapeutic strides have been made clinically in this form of cancer, little information on the biological and immunopathologic characteristics of HD has been reported. Two major questions in HD remain: (1)\the nature of the malignant cell and its relationship to the other "reactive" cells present in the polymorphous Hodgkin lesion and (2)\the cause of the characteristic cellular (T cell) immunologic defect seen in HD. We have recently hypothesized, based on our preliminary studies, that HD is a neoplasm of functional cells in the monocyte/macrophage lineage. We have shown that the putative neoplastic cells (Reed-Sternberg cells (RSC) and their mononuclear variants (HDC)) have markers consistent with this cellular origin and make soluble biologically active products (monokines) that can account for the histopathologic appearance of HD. These studies will focus on the further delineation of the phenotypic characteristics of RSC and HDC, the behavior of these cells in vitro, and their sensitivity to growth-promoting lymphokines secreted by immunoregulatory cells in their environment. We will attempt to establish long-term cell lines from the malignant cells. The second phase of the research will be to study the HD T-cell defect vis-a-vis the interleukin system of lymphoid-growth factors. Since these growth factors have been shown to control and regulate human T-cell function, we will evaluate the HD patients' ability to generate and react to interleukin growth factors to ascertain if the characteristic T-cell immunodeficiency can be correlated with an intrinsic defect in the interleukin system. These studies should provide important new data on two central issues in HD. (IP)